Assessing the treatment pattern,health care resource utilisation,and economic burden of multiple myeloma in France using the Système National des Données de Santé (SNDS) database: a retrospective cohort study

Background

Real-world data on health care resource utilisation (HCRU) and costs for French patients with multiple myeloma (MM) are limited due to the quickly evolving MM treatment landscape. This retrospective, national-level study quantified the MM economic burden in France.

Methods

The study included patients with newly diagnosed MM from the Système National des Données de Santé coverage claims database between 2013 and 2018 who received active treatment within 30 days of diagnosis. HCRU included hospitalisations, drugs, consultations, procedures, tests, devices, transport, and sick leave. Costs were annualized to 2019 prices. Drug treatments, reported by line of therapy (LOT), were algorithmically defined using drug regimen, duration of therapy, and gaps between treatments. Analyses were stratified by stem cell transplantation status and LOT.

Results

Among 6413 eligible patients, 6229 (97.1%) received ≥ 1 identifiable LOT; most received 1 (39.8%) or 2 LOT (27.5%) during follow-up. Average annual hospitalisation was 6.3 episodes/patient/year (median duration: 11.6 days). The average annual cost/patient was €58.3 K. Key cost drivers were treatment (€28.2 K; 39.5% of total HCRU within one year of MM diagnosis) and hospitalisations (€22.2 K; 48.6% of total HCRU costs in first year). Monthly treatment-related costs increased from LOT1 (€2.447 K) and LOT5 + (€7.026 K); only 9% of patients received LOT5 + . At LOT4 + , 37 distinct regimens were identified. Hospitalisation costs were higher in patients with stem cell transplantation than total population, particularly in the first year.

Conclusions

This study showed a high economic burden of MM in France (€72.37 K/patient/year in the first year) and the diversity of regimens used in late-line treatments.

     

The present and future burden of previously treated advanced non-small cell lung cancer (NSCLC) by histology and line of therapy in France,Germany, Italy,and Spain: model-based predictions

Background

The burden of advanced non-small cell lung cancer (NSCLC) is not well understood, and the number of patients likely to receive treatment in Europe has not been quantified. The aim of this study was to forecast the annual number of patients with squamous and non-squamous advanced NSCLC likely to receive second and third lines of therapy (LOT) from 2016 to 2020 in France, Germany, Italy, and Spain.

Methods

A patient count model (PCM) was developed in Microsoft Excel to estimate the number of patients with refractory advanced NSCLC eligible to receive systemic treatment. Using historical population-based cancer registry data, segmented linear regression (“Joinpoint”) was used to forecast age- and sex-stratified lung cancer incidence rates in each country through 2020. Yearly incident case count totals by country were apportioned according to NSCLC histology and stage at diagnosis. Country-specific treatment rates came from a recent medical chart review study, and early- to advanced-stage disease progression rates were estimated over a 10-year interval. A probabilistic sensitivity analysis (PSA) was performed to estimate variability in the patient counts.

Results

The combined number of squamous and non-squamous advanced NSCLC patients estimated to receive second and third LOT, respectively, in 2016 were France?=?11,600 and 3500; Germany?=?15,100 and 4900; Italy?=?13,500 and 2500; Spain?=?9400 and 2100. The forecasted numbers of patients receiving second and third LOT, respectively, in 2020 were France?=?13,900 and 4200; Germany?=?16,200 and 5200; Italy?=?15,100 and 2600; Spain?=?11,000 and 2500.

Conclusions

Driven by growth in the incidence of NSCLC among women, the model forecasts an overall increase in the number of patients with advanced-stage squamous and non-squamous NSCLC likely to receive systemic treatment in the year 2020. The results highlight the significant burden of refractory advanced NSCLC and the need for more robust surveillance data to accurately quantify the burden of disease.

     

Development of the Multiple Myeloma Symptom and Impact Questionnaire: A New Patient-Reported Outcome Instrument to Assess Symptom and Impacts in Patients With Multiple Myeloma

ObjectivesThis study aimed to develop and assess the content validity of a patient-reported outcomes (PROs) instrument to measure symptoms and impacts experienced by patients with active multiple myeloma (MM).MethodsThe PRO instrument was developed using an iterative, mixed-methods approach. The list of concepts was generated based on a review of existing evidence (qualitative studies and literature) and post hoc psychometric evaluations of 2 PRO instruments in 3 clinical trials. A total of 30 adult patients with MM from the United States participated in hybrid concept elicitation/cognitive debriefing interviews to validate the content validity of the newly developed PRO instrument. Translatability assessment was completed in 8 languages.ResultsThe item generation process resulted in 17 symptom and 9 impact concepts for evaluation. The concept elicitation interviews and analysis were based on the first 25 participants; evidence of saturation was observed. The cognitive debriefing interviews and analysis were based on the last 23 participants across 4 waves of interviews. On the basis patient feedback, 10 items were removed, and 1 item was added to the PRO instrument. The translatability assessment resulted in 1 minor revision. The multiple myeloma symptom and impact questionnaire (MySIm-Q) includes 11 symptom and 6 impact concepts, organized within 8 hypothesized subdomains, with each concept measured using a 5-point verbal rating scale and a 7-day recall period.ConclusionsThe MySIm-Q instrument was developed using rigorous and mixed methodology and with direct input from patients who received a diagnosis of MM. The MySIm-Q has good content validity and is culturally relevant for use in global clinical trials.     

The use of immune complex vaccines to enhance antibody responses against neutralizing epitopes on HIV-1 envelope gp120

The capacity of immune complexes to augment antibody (Ab) responses is well established. The enhancing effects of immune complexes have been attributed mainly to Fc-mediated adjuvant activity, while the ability of Abs to induce antigenic alterations of specific epitopes as a result of immune complex formation has been less well studied. Previously we have shown that the interaction of anti-CD4-binding site (CD4bs) Abs with HIV-1 gp120 induces conformation changes that lead to enhanced antigenicity and immunogenicity of neutralizing epitopes in the V3 loop. The present study shows that significant increases in the antigenicity of the V3 and C1 regions of gp120 were attained for several subtype B gp120s and a subtype C gp120 upon immune complex formation with the anti-CD4bs monoclonal Ab (mAb) 654-D. Such enhancement was observed with immune complexes made with other anti-CD4bs mAbs and anti-V2 mAbs, but not with anti-C2 mAbs, indicating this activity is determined by antigen specificity of the mAb that formed the immune complex. When immune complexes of gp120_LAI/654-D and gp120_JRFL/654-D were tested as immunogens in mice, serum Abs to gp120 and V3 were generated at significantly higher titers than those induced by the respective uncomplexed gp120s. Notably, the anti-V3 Ab responses had distinct fine specificities; gp120_JRFL/654-D stimulated more cross-reactive anti-V3 Abs than gp120_LAI/654-D. Neutralizing activities against viruses with heterologous envelope were also detected in sera of mice immunized with gp120_JRFL/654-D, although the neutralization breadth was still limited. Overall this study shows the potential use of gp120/Ab complexes to augment the immunogenicity of HIV-1 envelope gp120, but further improvements are needed to elicit virus-neutralizing Ab responses with higher potency and breadth.     

Patient and Caregiver Experience Decision Factors in Treatment Decision Making: Results of a Systematic Literature Review of Multiple Myeloma Decision Aids

ObjectivesDecision-aids (DAs) may facilitate shared decision-making for patients and caregivers, by providing evidence-based information to assist healthcare professionals, patients, and caregivers in making choices about aspects of care, and/or highlighting decision factors to discuss with the potential of altering the treatment decision. These decision factors may not be well integrated in DAs.MethodsA systematic literature review was conducted in the field of multiple myeloma (MM) on peer-reviewed publications, extended with a gray literature search. Data on whether and how patient and caregiver experience elements, other than survival and physical quality of life, were mentioned as decision factors in the identified MM DAs were extracted and analyzed qualitatively.ResultsSeventy MM DAs were found and analyzed; 51% of DAs mentioned any patient non-routinely assessed experience decision factors and only 17% mentioned any caregiver-related information. One hundred and forty potential decision factors were extracted, deduplicated and categorized into the following categories: 1) financial, 2) mode of administration / transportation issues, 3) personal beliefs and values, 4) emotional and social quality of life, 5) other medical information, 6) availability of social support, 7) caregiver burden. None of the DAs presented a comprehensive framework on all seven categories of decision factors being consider when mapping patient and caregiver experience value elements in MM.ConclusionsBased on available DAs, we recommend a set of patient and caregiver experience decision factors that have the potential to affect treatment choices of patients with MM, which should be included in DAs, including MM clinical guidelines.     

Transarterial Chemoembolization Treatment: Association between Multiple Treatments,Cumulative Expenditures,and Survival

ObjectivesTo examine cumulative survival and Medicaid-paid expenses associated with multiple courses of transarterial chemoembolization (TACE) as primary treatment for hepatocellular carcinoma (HCC).MethodsMedicare enrollees diagnosed with primary HCC from 2000 to 2007, ever treated with TACE, but not transplant/resection, followed through 2009 by using the Surveillance, Epidemiology and End-Results Program and linked Medicare databases. Cumulative all-cause/HCC-related survival was estimated by using multivariate Cox proportional hazards models stratified by the total number of TACE treatments. Multivariate weighted Cox regressions estimated the average risk of mortality faced with nonproportional hazards. Lin’s inverse probability-weighted least squares regression method estimated cumulative Medicare expenditures adjusted for censoring and covariates.ResultsOf 1228 patients, 34% were stage 1, 16% stage 2, 19% stage 3, 6% stage 4, and 26% unstaged. About 44% were aged 65 to 75 years, 69% were men, and 72% were Caucasian. Over half (57%) of the patients received one course, 24% two, 11% three, and 8% four courses of TACE. One-course patients incurred an average $74,788 (95% confidence interval [CI] $71,890–$77,686), two-course patients $101,126 (95% CI $94,395–$107,856), three-course patients $111,776 (95% CI $101,931–$121,621), and four-plus-course patients $148,878 (95% CI $136,346–$161,409). One-course patients lived (all-cause) an average 1.86 (95% CI 1.82–1.90), two-course patients 2.09 (95% CI 2.05–2.13), three-course patients 2.81 (95% CI 2.66–2.97), and four-plus-course patients 3.06 (95% CI 2.95–3.18) years after diagnosis. Average risk of all-cause mortality was not significantly different between one/two courses or three/four-plus courses.ConclusionsCumulative Medicare expenditures nearly doubled from one-course to four-plus-course patients. On average, four-plus-course patients lived over one more year than did one-course patients. Physician/patient decisions should be balanced with consideration of efficient use of limited resources, but payer’s intervention in physician discretion may not be important in this setting.     

实验室感染肾综合征出血热4例报告

肾综合征出血热(HFRS)传染源主要为野生的啮齿类动物。但是，国内外动物实验室、动物饲养室人员感染HFRS病毒的事件屡有发生。2005年初在牡丹江地区某高校动物实验室发生4例实验动物Wister大白鼠传染的HFRS，现报告如下。     

Stratified treatment recommendation or one-size-fits-all? A health economic insight based on graphical exploration

Objectives

We sought to explore to what extent the use of Subpopulation Treatment Effect Pattern Plot (STEPP) may help to identify efficient treatment allocation strategy.

Methods

The analysis was based on data from the COACH study, in which 1023 patients with heart failure were randomly assigned to three treatments: care-as-usual, basic support, and intensive support. First, using predicted 18-month mortality risk as the stratification basis, a suitable strategy for assigning different treatments to different risk groups of patients was developed. To that end, a graphical exploration of the difference in net monetary benefit (NMB) across treatment regimens and baseline risk was used. Next, the efficiency gains resulting from this proposed subgroup strategy were quantified by computing the difference in NMB between our stratified approach and the best performing population-wide strategy.

Results

The analysis using STEPPs suggested that a differentiated approach, based on offering intensive support to low-risk patients (18-month mortality risk ≤ 0.16) and basic support to intermediate- to high-risk patients (18-month mortality risk > 0.16) would be an economically efficient treatment allocation strategy. This was confirmed in the subsequent cost-effectiveness analysis, where the average gain in NMB resulting from the proposed stratified approach compared to basic support for all was found to be €1312 (95% CI €390–€2346) per patient.

Conclusions

STEPP provides a systematic approach to assess the interaction between baseline risk and the difference in NMB between competing interventions and to identify cutoffs to stratify patients in a health economically optimal manner.

     

Transdermal delivery of plasmid encoding truncated nucleocapsid protein enhanced PRRSV-specific immune responses

BackgroundPorcine Reproductive and Respiratory Syndrome virus (PRRSV) induces several immunomodulatory mechanisms that resulted in delayed and ineffective anti-viral immune responses. Recently, it has been shown that intradermal immunization of plasmid encoding truncated nucleocapsid protein (pORF7t) could reduce PRRSV-induced immunomodulatory activities and enhances anti-PRRSV immunity in vaccinated pigs. However, intradermal immunization may not be practical for farm setting. Currently, there are several transdermal delivery systems available in the market, although they were not originally designed for plasmid delivery.ObjectivesTo investigate the potential use of a transdermal delivery system for delivering of pORF7t and its immunological outcomes.MethodThe immunomodulatory effects induced by transdermal delivery of pORF7t were compared with intradermal immunization in an experimental pig model. In addition, immunomodulatory effects of the DNA vaccine were determined in the fattening pigs kept in a PRRSV-positive farm environment, and in the experimental pigs receiving heterologous prime-boost, pORF7t-modified live vaccine (MLV) immunization.ResultThe patterns of PRRSV-specific cellular responses induced by transdermal and intradermal immunizations of pORF7t were similar. Interestingly, the pigs transdermally immunized with pORF7t exhibited higher number of PRRSV-specific CD8⁺IFN-γ⁺ cells. Pigs immunized with pORF7t and kept at PRRSV-positive environment exhibited enhanced PRRSV-specific IFN-γ⁺ production, reduced numbers of regulatory T lymphocytes (Tregs) and lower lung scores at the end of the finishing period. In the heterologous prime-boost experiment, priming with pORF7t prior to MLV vaccination resulted in significantly higher numbers of CD3⁺IFN-γ⁺ subpopulations, lower numbers of PRRSV-specific CD3⁺IL-10⁺ cells and Tregs, and rapid antibody responses in immunized pigs.ConclusionTransdermal immunization with pORF7t reduced PRRRSV-induced immunomodulatory effects and enhanced long-term PRRSV-specific cellular responses in vaccinated pigs. Furthermore, heterologous DNA-MLV prime-boost immunization significantly improved the quality of PRRSV-specific cellular and humoral immunity. The information could benefit the future development of PRRSV management and control strategies.     

Policymaker,Please Consider Your Needs Carefully: Does Outcomes Research in Relapsed or Refractory Multiple Myeloma Reduce Policymaker Uncertainty Regarding Value for Money of Bortezomib?

IntroductionDutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding.MethodsOur cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals.ResultsAll patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793–€229,783) and €52,760 (range €748–€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate.ConclusionsIt was possible to develop evidence on bortezomib’s use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.     

Clinical efficacy of pneumococcal vaccination in multiple myeloma patients on novel agents: Results of a prospective clinical study

IntroductionAmong the high risk groups, patients with multiple myeloma (MM) have one of the highest incidence of invasive pneumococcal disease, mainly pneumonias. Recent changes in MM treatment have now led to an increase of survival, while the infection-related mortality remains high. The question of efficacy of pneumococcal vaccination in patients receiving novel target agents has not been clinically investigated before.Patients and methodsWe have introduced the 3-dose vaccination regimen by 13-valent pneumococcal conjugate (PCV13) vaccine between the treatment courses with novel target agents (bortezomib, lenalidomide, ixazomib) with a minimum of 1 month interval. The incidence of pneumonias during the one-year observation period was taken as a primary outcome in this registered clinical trial.ResultsFrom 2017 to 2020, we have prospectively included 18 adult patients who were vaccinated by PCV13 along with 18 patients of a control matched group. No adverse effects of vaccination were registered in the study. We have observed an independent effect of PCV13 vaccination on the incidence of pneumonias. The absolute risk reduction of pneumonias in patients received PCV13 vaccination was 33.3%. Number needed to treat for PCV13 vaccination in multiple myeloma patients receiving novel agents was 3.0; (95% CI 1.61–22.1; p = 0.0571).ConclusionTherefore, we have shown the clinical effectiveness of PCV13 vaccination schedule based on 3 doses given with a minimum 1 month interval between the courses of novel agents in multiple myeloma patients, despite the expected decrease in immunological response to vaccination during target and immunotherapy. ClinicalTrials.gov Identifier: NCT03619252.     

Effectiveness of recombinant zoster vaccine (RZV) in patients with inflammatory bowel disease

Background and AimsPatients with Inflammatory bowel disease (IBD) are at an increased risk of developing herpes zoster (HZ). The effectiveness of the recombinant zoster vaccine (RZV) in patients with IBD is unknown.MethodsIn this retrospective cohort study using Explorys (October 2017–April 2020; IBM Corporation, Somers, NY, USA), the effectiveness of RZV for the prevention of HZ in patients with IBD ≥ 50 years was compared to general population aged ≥ 50 years. Rates of de-novo HZ were compared between patients with IBD and the general population and stratified by number of RZV doses received. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).ResultsThe overall proportion of IBD patients ≥ 50 years who received HZ vaccination with the live zoster vaccine (ZVL) or RZV was low (n = 11320, out of 112,200 IBD patients in the cohort). A total of 1670 patients received RZV. Receipt of the RZV resulted in a significantly lower rate of HZ in IBD patients (OR 0.36, 95% CI 0.23–0.56) compared to the general population (OR 0.74, 95% CI 0.59–0.92). However, despite vaccination, patients with IBD who received the RZV were still 3-times more likely to develop HZ during the study follow up period compared to the general population receiving the RZV (OR 3.06, 95% CI 1.87–5.02) and unvaccinated IBD patients were 6-times more likely to develop HZ compared to general population (OR 6.21, 95% CI 6.02–6.41).ConclusionThe recombinant zoster vaccine is effective in reducing the risk of HZ in patients with IBD compared to the general population. During our follow up period, patients with IBD, however, still remain at an increased risk for HZ despite vaccination.     

Value of Reducing Wait Times for Chimeric Antigen Receptor T-Cell Treatment: Evidence From Randomized Controlled Trial Data on Tisagenlecleucel for Diffuse Large B-Cell Lymphoma

ObjectivesThis study aimed to quantify the value of reducing chimeric antigen receptor T-cell (CAR-T) treatment wait times on patients with refractory and relapsed aggressive blood cancer who can newly gain access to treatment or access treatment earlier in their disease course.MethodsUsing data from the JULIET clinical trial, we first identified the number of additional patients with diffuse large B-cell lymphoma that would have been treated with tisagenlecleucel CAR-T therapy if wait times were shortened. For these patients, we estimated mortality benefits using literature estimates of CAR-T effectiveness. Next, among patients who already received CAR-T, we estimated tumor burden progression over time using a linear probability regression model. The primary outcome variable was an indicator for having above-normal lactate dehydrogenase, and we controlled for time, use of bridging therapy, and time-invariant patient characteristics. The regression results, along with literature estimates relating lactate dehydrogenase to CAR-T effectiveness, were used to compute the survival benefits of earlier CAR-T treatment.ResultsReducing wait times by 2 months increased the number of eligible patients receiving CAR-T by at least 10.7%. For patients already receiving tisagenlecleucel CAR-T, a 2-month reduction in wait times generated a 3.3% increase in survival gains per treated patient. Thus, among patients seeking treatment, the combined treatment efficacy increased by 14%, with approximately one-quarter of survival benefits accruing to existing patients receiving faster treatment.ConclusionsDelays affected not only access to CAR-T treatments but also treatment effectiveness. Our results highlight the survival benefits of expediting treatment access and may help explain some observed differences in CAR-T effectiveness across countries.     

Apple polyphenol protects against cigarette smoke-induced acute lung injury

ObjectiveChronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving oxidative stress as well as a wide variety of cells activated from smoking cigarettes. There have been disappointingly few therapeutic advances in drug therapy for COPD. Plant polyphenols have been the topic of much research regarding their antioxidant activities and antiinflammatory and immunomodulatory effects. In the present study, we ask whether apple polyphenol provides protection against cigarette smoke (CS)-induced acute lung injury.MethodsICR mice were exposed to CS for 4 d with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with apple polyphenol (APP) by gavage; all examinations were performed 18 h after the last CS exposure.ResultsAPP at 30, 100, or 300 mg not only significantly dose-dependently reduced the CS-induced accumulation of inflammatory cells and gene/protein expression of proinflammatory factors both in the lung and in bronchoalveolar lavage fluid, but also significantly reversed oxidative stress in the lungs. Additionally, treatment with APP also significantly regulated the CS-induced imbalance of matrix metalloproteinases-9/tissue inhibitor of metalloproteinase-1 expression in the lungs. To investigate further the possible signaling pathway of APP effects, we examined protein expression of p-P38 MAPK by immunohistochemistry that found treatment with APP significantly decreased the CS-induced increases of p-P38 expression in the lungs.ConclusionTaken together, APP may be a potential dietary nutrient supplement agent to improve quality of life of COPD patients by inhibiting CS-exposed acute lung injury via P38 MAPK signaling pathway.     

早期宫颈癌保留卵巢内分泌功能的临床研究

目的:探讨早期宫颈鳞癌患者行宫颈癌根治术[原位保留双侧卵巢或行侧面卵巢移位术(LOT)]后对卵巢内分泌功能的影响。方法:选取年龄<45岁、病灶<2 cm、FIGO分期为IA2～IB1、未发现区域淋巴结转移的27例宫颈鳞癌患者,其中手术时行LOT的23例,卵巢原位保留的4例,测定患者术前、术后的血清女性激素水平。结果:LOT后未放疗组16例患者术后6个月FSH、LH、E2水平及Kupperman评分与术前比较差异无统计学意义(P>0.05):LOT后放疗组7例患者术后6个月FSH、LH水平、Kupperman评分与术前比较差异有统计学意义(P<0.05);LOT后放疗组FSH、LH、Kupperman评分高于未放疗组(P<0.05),低于原位保留放疗组4例(P<0.05);LOT的手术年龄在40～45岁的9例患者中,卵巢功能正常3例,卵巢功能减退6例;<40岁的患者14例中,卵巢功能正常10例,卵巢功能减退4例。两组均无卵巢功能丧失,两组间卵巢功能正常的比例无显著差异(P>0.05)。结论:年轻宫颈鳞癌患者行宫颈癌手术并LOT时,术后如果不行放疗,卵巢内分泌功能保留良好;放疗对宫颈癌手术时移位的卵巢有一定影响,并不能完全避开放射线的照射,但卵巢移位对宫颈癌手术后患者的卵巢内分泌功能起到了很大的保护作用。手术年龄超过40岁的患者仍然可以从LOT获益。     

Targeting the tumor microenvironment with anti-neu/anti-CD40 conjugated nanoparticles for the induction of antitumor immune responses

Clinical and preclinical data indicate that immunotherapeutic interventions could induce immune responses capable of controlling or retard the tumor growth. However, immunotherapies need to be further optimized. We hypothesized that a more effective strategy for tumor eradication is to directly target the tumor microenvironment in order to generate a proinflammatory response and induce a localized antitumor immune response capable of eliminating the tumor cells. Nanoparticles have been proven to be an effective delivery system. In these studies we evaluated conjugated anti-RNEU and anti-CD40 antibodies onto PLA-(poly dl-lactic acid)-biodegradable nanoparticles (PLA-NP) for the induction of antitumor immune responses. The anti-neu/anti-CD40-NP were functional in vitro recognizing RNEU⁺ tumors and activating dendritic cells. The delivery of anti-neu/anti-CD40-NP but not anti-neu-NP or anti-CD40-NP induced an antitumor response resulting in complete tumor elimination and generation of protective memory responses. The anti-neu/anti-CD40-NP specifically activated an antitumor response against RNEU⁺ tumors but not against RNEU⁻ tumors. The antitumor immune responses correlate with the induction of a Th1-proinflammatory response, reduction in the number of Tregs within the tumor and activation of a specific cytotoxic response. These results indicate that anti-neu/anti-CD40-NP with immunomodulatory properties are safe and can be used effectively as cancer vaccines strategy for the specific induction of antitumor immune responses.     

Prevalence of meningococcal meningitis in China from 2005 to 2010

BackgroundWe aimed to estimate the prevalence and epidemiologic characteristics of meningococcal meningitis (MM) in mainland China (excluding Taiwan, Hong Kong, and Macau) and to provide reference data for controlling the outbreak and prevalence of MM.MethodsData from the National Notifiable Diseases Registry System and the MM case information reporting system from 2005 to 2010 as well as data from the MM Surveillance System were used.ResultsThe morbidity of MM for the whole country was, on average, 0.09 cases per 100,000 (range 0.02 [2010]–0.18 [2005] cases per 100,000) from 2005 to 2010, the incidence rate was highest in the Xinjiang autonomous region (average 0.56 cases per 100,000), and the majority of cases came from Anhui province (average 0.32 cases per 100,000). Morbidity was highest in children under 1 year old (average 0.60 cases per 100,000). The proportion of laboratory-confirmed cases of serogroups A, B, and C were 37.2, 11.5 and 42.7, respectively, from 2005 to 2010.ConclusionsThe incidence level declined year-to-year in mainland China. Children and students are the most at risk groups. The proportion of serogroup C cases has increased year-to-year, and new cases of serogroup W135 have been found. Controlling the epidemic of serogroup C and preventing outbreaks of serogroup B and W135 represent major future challenges.